Abstract P3-14-06: Residual tumor autophagy marker LC3B is a prognostic marker in local advanced breast cancer underwent neoadjuvant chemotherapy

Abstract

Abstract Purpose A membrane-bound microtubule-associated protein chain 3B(LC3B) is known as one of the most specific biomarker for autophagy. The goal of this study is to investigate the prognostic value of autophagy marker LC3B in patients with residual tumors after neoadjuvant chemotherapy(NCT) for local advanced breast cancer(LABC) Patients and Methods Expression of LC3B in residual breast cancer cells were assessed by immunohistochemistry in surgical specimens from 229 patients who were diagnosed with histological proven invasive breast cancer. All patients had undergone neoadjuvant chemotherapy followed by mastectomy, and were considered as non pathological complete responders(non-pCR)after pathological evaluation. The density of positive staining of LC3B was measured with the use of a computerized image system. Prognostic value of various clinicopathologic factors was combined and evaluated by using Cox regression model. Results LC3B density was similar in the peripheral and central area of tumor(P = 0.328), however, it was siginifcantly lower in the extratumoral area(P<0.001 and P<0.001, respectively). High LC3B density was more likely to be observed in patients with PR-negative at diagnosis(P = 0.033), Beclin-1-positive(P<0.001) at surgery and higher Ki-67 index at surgery(P = 0.029). Breast cancer subtype was also correlated to LC3B expression(P = 0.003), an obvious lower proportion of LC3B-high density was detected in luminal-A patients than in other subtypes(32.4% in luminal-A, 59.4% in luminal-B, 65.4% in HER-2+, and 46.7% in TNBC). In survival analysis, only LC3B and residual nodal status after NCT resulted significant predictors of both RFS(HR = 1.180,P = 0.012 and HR = 3.067, 6.103, P<0.001, respectively) and overall survival(HR = 2.428, P = 0.008 and HR = 1.809,4.283, P = 0.003, respectively). Ki-67 was also an indepentent predictor for RFS(HR = 1.122, P = 0.019). The prognostic value of LC3B was most significant in triple-negative patients than in other subtypes. With a combination of LC3B expression and status of residual involved lymph nodes, patients were classified into four groups with different risk of relapse and death(P<0.001 for RFS and P = 0.003 for OS). Patients with no positive node residual and low LC3B expression were at low risk of relapse and death, with 5-year RFS and OS of 97% and 97%, respectively. However, the 5-year RFS and OS for patients with a positive node satus and high LC3B were only 52% and 66%, respectively. Conclusion LC3B is a prognostic marker in non-pCR patient after neoadjuvant chemotherapy for breast cancer, which highlighting the importance of autophagy in the biological behavior of chemo-resistence cancer cells. Evaluating and targeting autophagy in neoadjuvant setting may help in prevention of disease relapse in non-pCR patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-06.